March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
SIRT1 Mediated Mitochondrial Biogenesis for The Protection of RGC-5 Cell During Oxidative Stress
Author Affiliations & Notes
  • Qian Fan
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Shida Chen
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Jian Ge
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Xiulan Zhang
    Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
  • Footnotes
    Commercial Relationships  Qian Fan, None; Shida Chen, None; Jian Ge, None; Xiulan Zhang, None
  • Footnotes
    Support  National Natural Science Foundation of China (30872831), Doctoral Fund of Ministry of Education of China (20100171110077) and Guangdong Provincial Natural Science Foundation (S2011020002401).
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6582. doi:
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      Qian Fan, Shida Chen, Jian Ge, Xiulan Zhang; SIRT1 Mediated Mitochondrial Biogenesis for The Protection of RGC-5 Cell During Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6582.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Glaucoma is increasingly recognized as a neurodegenerative disorder, and age-related mitochondrial dysfunction is believed to contribute to the loss of retinal ganglion cells in glaucoma. SIRT1 is a member of a conserved gene family (sirtuins) encoding NAD+-dependent deacetylases. SIRT1 deacetylase many target proteins including the PGC-1α, which may increase the co-activation of its target transcription factors involved in the mitochondrial biogenesis, and turnover protect the cell from apoptosis. We hypothesize that SIRT1 involves in the loss of retinal ganglion cells in the glaucoma and regulating SIRT1 will improve the mitochondrial function which in turn protects the retinal ganglion cells.

Methods: : Cultured RGC-5 cells were stressed by removal of serum for 1-72 hrs, the apoptosis of the cells was detected by Hoechst, and cells were harvested for protein extraction to detect the expression of SIRT1. RGC-5 cells were subjected to serum deprivation or with resveratrol (an SIRT1 agonist), Nicotinamide (an SIRT1 antagonist) for 24 hrs, the expression of the caspase-3, cytochrome c, TFAM (a key factor involved in the mitochondrial biogenesis) and SIRT1 were detected by western blot.

Results: : Serum deprivation induced RGC-5 cells loss was related to the increased expression of caspase-3 and cytochrome c. SIRT1 increased significantly at the 6hrs of the serum deprivation. Treatment with resveratrol increased the SIRT1, TFAM expression, decreased the expression of cytochrome c, which protected the RGC-5 from apoptosis, while Nicotinamide play the opposite effect.

Conclusions: : Mitochondrial dysfunction was involved in the RGC-5 apoptosis during the serum deprivation. Increased expression of SIRT1 protects the RGC-5 from apoptosis through increasing the expression of TFAM. Although the exact mechanism of the mitochondrial biogenesis involved in the protection of RGC remained unknown, these results supported the hypothesis that SIRT1 played a key role in the protection of RGC-5 through the mitochondrial biogenesis.

Keywords: apoptosis/cell death • neuroprotection • oxidation/oxidative or free radical damage 
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